1. Field of the Invention
The subject invention is directed to using pharmacological quantities of hormones to prevent the development of atherosclerosis and, more particularly, to the administration of dehydroepiandrosterone (DHEA) for beneficial effects in human beings.
2. Description of the Prior Art
Cholesterol plays an essential role in the body in building cell membranes, in sex hormones, and in aiding digestion. Cholesterol is produced in the liver and transported to cells via the bloodstream, but it may also be obtained directly from fatty foods typically found in western diets. The low density lipoprotein (LDL) carrier particles carry 60-80% of the blood's total cholesterol. An excess of LDL carrier particles may lead to plaque build up on the interior walls of coronary arteries.
Blockage of the artery causes angina (chest pain) and over time, large build ups can lead to heart attacks. The condition of having plaque on the artery walls is refereed to as atherosclerosis. Severe cases of atherosclerosis are treated by mechanically compressing the plaque on the walls with an inflatable balloon by balloon angioplasty. The high density lipoprotein (HDL) carrier particles remove excess cholesterol from the blood and tissue cells and may collect cholesterol from plaque, thus reversing the process of "narrowing" the artery. For those at risk, the typical approach for correcting problems associated with plaque build up is to decrease the total cholesterol level. This may be done using any of a variety of well known methods including changing one's diet.
DHEA is the most abundantly produced adrenal steroid, and serum concentrations of its sulfate ester, DHEA sulfate (DHEA-S), are approximately twenty fold higher than those of any other circulating steroid hormone. Peak serum DHEA and DHEA-S levels occurs when patients are approximately twenty-five years old. The serum levels decrease with age and are approximately five percent of the peak level when patients are between eighty-five and ninety years old. Both DHEA and DHEA-S can be converted to testosterone. All tissues studied to date contain steroid sulfatases which readily convert DHEA-S to DHEA, and DHEA have a high turnover rate. Despite the abundance and rapid turnover of the hormone, the physiological role of DHEA is unknown.
In Geriatrics 37: 157 (1982), DHEA was reported to be a "miracle drug" which may prevent obesity, aging, diabetes mellitus and heart disease. These assertions stem from animal studies which demonstrated that DHEA administration resulted in lower body weight in C3H(Avy/a) mice without affecting appetite or food intake, prevented the development of diabetes in genetically diabetic (-db/db) or obese (-ob/ob) mice, increased tissue sensitivity to insulin in aged normal mice, and prevented the rise in cholesterol levels of rats made hypothyroid with propylthiouracil. Human studies have revealed an inverse correlation between fetal serum DHEA-S and low density lipoprotein (LDL) levels (Parker et al, Science 208: 512 (1980)), and an inverse relationship between cardiovascular death and serum DHEA-S levels in adult men (Barrett-Connor et al, N. Engl. J. Med., 315: 1519 (1986). DHEA was widely used in this country for weight loss, longevity and sex life enhancement purposes until it was recently banned for nonprescription sales by the Food and Drug Administration.
U.S. Pat. No. 4,602,008 to Krsek, U.S. Pat. No. 4,666,898 to Coleman et al, and U.S. Pat. No. 4,680,289 to Applezweig show synthesized metabolites of DHEA called etiocholanolones which are used to treat obesity. These metabolities are not converted into sex hormones by the body. It is believed that a balance exists in the body between DHEA and cortisol. DHEA tends to limit production of stored compounds like fat, while cortisol promotes such production. As the level of DHEA declines with age, so does its opposing effect to cortisol. This decline leads to the chronic diseases of aging, including atherosclerosis, diabetes, obesity and cancer. Studies using mice have shown that obese mice treated with ethiocholanolones can attain their normal weight in a short period of time.